Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA.
Infectious Disease and Pathogenesis Section, Comparative Medicine Branch, NIAID, NIH, Rockville, Maryland, USA.
JCI Insight. 2018 May 3;3(9):120608. doi: 10.1172/jci.insight.120608.
The underlying pathology of atopic dermatitis (AD) includes impaired skin barrier function, susceptibility to Staphylococcus aureus skin infection, immune dysregulation, and cutaneous dysbiosis. Our recent investigation into the potential role of Gram-negative skin bacteria in AD revealed that isolates of one particular commensal, Roseomonas mucosa, collected from healthy volunteers (HVs) improved outcomes in mouse and cell culture models of AD. In contrast, isolates of R. mucosa from patients with AD worsened outcomes in these models. These preclinical results suggested that interventions targeting the microbiome could provide therapeutic benefit for patients with AD. As a first test of this hypothesis in humans, 10 adult and 5 pediatric patients were enrolled in an open-label phase I/II safety and activity trial (the Beginning Assessment of Cutaneous Treatment Efficacy for Roseomonas in Atopic Dermatitis trial; BACTERiAD I/II). Treatment with R. mucosa was associated with significant decreases in measures of disease severity, topical steroid requirement, and S. aureus burden. There were no adverse events or treatment complications. We additionally evaluated differentiating bacterial metabolites and topical exposures that may contribute to the skin dysbiosis associated with AD and/or influence future microbiome-based treatments. These early results support continued evaluation of R. mucosa therapy with a placebo-controlled trial.
特应性皮炎（AD）的潜在病理学包括皮肤屏障功能受损、金黄色葡萄球菌皮肤感染易感性、免疫失调和皮肤微生态失调。我们最近对革兰氏阴性皮肤细菌在 AD 中的潜在作用进行了调查，结果表明，从健康志愿者（HV）中分离出的一种特定共生菌玫瑰单胞菌（Roseomonas mucosa），在 AD 的小鼠和细胞培养模型中改善了疾病结局。相比之下，AD 患者分离出的 R. mucosa 在这些模型中恶化了疾病结局。这些临床前结果表明，针对微生物组的干预措施可能为 AD 患者提供治疗益处。作为在人类中对此假说的首次检验，10 名成年患者和 5 名儿科患者参加了一项开放标签 I/II 期安全性和疗效试验（针对特应性皮炎中玫瑰单胞菌的皮肤治疗效果的初步评估试验；BACTERiAD I/II）。使用 R. mucosa 治疗与疾病严重程度、局部类固醇需求和金黄色葡萄球菌负担的显著降低相关。没有不良反应或治疗并发症。我们还评估了可能导致与 AD 相关的皮肤微生态失调并影响未来基于微生物组的治疗的差异细菌代谢物和局部暴露。这些早期结果支持继续进行安慰剂对照试验，以评估 R. mucosa 治疗的效果。
